Laryngeal transplantation in the setting of cancer: a rat model.
OBJECTIVE
Traditional immunosuppressive regimens make laryngeal transplantation in cancer patients prohibitive because of the increased risk of recurrence. Everolimus, a recently developed immunosuppressant, has demonstrated significant antitumor properties. The purpose of this study was to examine the effects of everolimus alone and in combination with other immunosuppressants on tumor growth in a combined laryngeal transplantation and tumor model.


METHODS
Animal, prospective, randomized, controlled, and blinded.


METHODS
One million squamous cell carcinoma cells (SCC-158) were injected intravenously into a total of 40 rats 1 day before laryngeal transplantation. Rats were divided into four groups differing by immunosuppressive regimens. Lung surface metastases were counted 21 days after inoculation, and numerical transplantation rejection scores were recorded. A separate experiment for comparison was performed with no transplant on 24 rats, but with the same immunosuppressive treatment groups.


RESULTS
The median number of lung surface metastases were: a) control (i.e., no immunosuppression): 85; b) everolimus 1.0 mg/kg: 25; c) tacrolimus 1.2 mg/kg: 1650; d) everolimus 1.0 mg/kg + tacrolimus 0.05 mg/kg: 1300. Rats receiving everolimus alone showed a statistically significant decrease in pulmonary surface metastases compared with the other groups. Transplanted rats had no difference in their outcomes when compared with non-transplanted rats.


CONCLUSIONS
Everolimus significantly decreases SCC-158 growth in our combined transplantation and tumor model compared with controls and other immunosuppressants.
Shipchandler
Taha Z
TZ
Head and Neck Institute, Cleveland Clinic, Cleveland, OH 44195, USA. shipcht@ccf.org
Lorenz
Robert R
RR
Lee
Walter T
WT
Teker
Aysenur Meric
AM
Dan
Olivia
O
Strome
Marshall
M
D000284:Administration, Oral; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000473:pathology / Q000556:secondary / Q000601:surgery*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D000068338:Everolimus; D006085:Graft Survival / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007822:Laryngeal Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000601:surgery*; D007825:Laryngectomy; D007830:Larynx / Q000637:transplantation*; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000139:chemically induced* / Q000473:pathology / Q000601:surgery; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D016559:Tacrolimus / Q000633:toxicity
D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus; D016559:Tacrolimus